Dr. Seshu’s research interests focus on two infectious diseases, Lyme Disease and Q fever.
Lyme Disease
Lyme Disease is the most prevalent arthropod-borne infectious disease in the US. Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to humans (and to other mammals) by the bite of infected ticks. This spirochetal pathogen rapidly alters its gene expression depending on the feeding status of the ticks and upon transmission to mammalian hosts. The lab’s current research interests are directed towards:
Determining the role of linear plasmid 54 (lp54) encoded genes of B. burgdorferi in the infectivity of mammalian hosts.
Characterization of the mechanisms of interactions of B. burgdorferi with mammalianhost cell surfaces.
Regulation of gene expression in B. burgdorferi-determining the contributions of Carbon storage regulator A (CsrABb) in modulating signal-dependent gene expression in B. burgdorferi and its interactions with other borrelial regulators of gene expression.
Metabolomics of B. burgdorferi facilitating its adaptation to host-specific conditions.
Q Fever
Q fever is caused by Coxiella burnetii, an obligate, intracellular pathogen. Acute Q fever is a self-limiting flu-like illness and is readily amenable to treatment with antibiotics. Chronic Q fever, on the other hand, is not easily treated with antibiotics and results in endocarditis, hepatitis, and pneumonia. C. burnetii with phase I LPS is highly infectious, disseminated as an aerosol, and capable of withstanding harsh environmental conditions. C. burnetii resides and replicates within the phagolysosomal vacuoles of macrophages and hence has a unique niche protected from the neutralizing effects of humoral immune response. A potent cell-mediated immunity is required to clear this intracellular acidophile. C. burnetii with phase II LPS is avirulent and serves as an excellent tool to study the intracellular trafficking kinetics of this pathogen using a variety of eukaryotic cells. The lab’s current research efforts are therefore directed towards:
Identification of T cell epitopes of C. burnetii.
Modification of select C. burnetii antigens to enhance protective T cell response against C. burnetii.
Generation of targeted deletion mutants of Phase II C. burnetii for study intracellular trafficking kinetics in eukaryotic cells/cell lines.